Uses of magnetic nanoparticles (MNPs) in vivo and/or in vitro are limited by such undesirable characteristics as poor colloidal stability, rapid opsonization and clearance by mononuclear phagocyte systems (MPS), poor targeting to cellular receptors, and nonspecific biofouling. Current methods for making magnetic nanoparticles employ a basic method for grafting poly(ethylene glycol) (PEG) moieties onto MNP surfaces (referred to as “PEGylation”), so as to reduce biofouling. However, current methods, such as attaching PEG to carboxylic acids on the surface of the nanoparticles using carbodiimide cross-linking chemistry, do not achieve sufficient PEG density to obtain a PEG “brush” layer, a dense layer in which the PEG chains extend away from the surface and provide optimal defense against opsonization, MNP colloid stability, and ample attachment sites for functionalization. Instead, the methods in use today result in a “mushroom” configuration of PEG, which promotes nonspecific binding.
It is therefore desirable to be able to sufficiently graft MNPs with a PEG passivation layer in a manner that allows for MNP functionalization, stability, targeting specificity, and anti-biofouling.